Unlocking the power of flow biocatalysis for the preparation of high-value natural and nature-inspired polyphenols

Introduction: Food-derived phenolic compounds are well known for their antioxidant and antimicrobial effects.1 Because of their hydrophilic nature and their intrinsic stability and bioavailability issues, their use as active ingredients is limited. Lipophilization of phenolic derivatives is a valid strategy to obtain amphiphilic compounds that can be used as multifunctional additives.2 Biocatalytic processes in continuous flow reactors represent an outstanding tool for the production of these active compounds. Material & Methods: Immobilised lipase B from Candida antarctica (CaLB) and tyrosinase from Agaricus Bisporus were the employed biocatalysts. Different green solvents were selected as unconventional reaction medium with low environmental impact. Results: Starting from tyrosol, a biocatalysed continuous process was developed for the synthesis of hydroxytyrosol. Together with other natural phenolics, they were lipophilised as esters, carbonates and carbamates through continuous-flow biocatalysed processes. The use of imm-CaLB as biocatalyst allowed to selectively react the primary alcohols leaving unreacted the phenol(s), which are fundamental for the antioxidant activity. The amphiphilic derivatives retained their radical scavanger properties and preserved or imporved their antimicrobial activity, while their lipophilicity was increased. Conclusion: A versatile and efficient biocatalysed flow protocol for the synthesis of a series of bioactive phenolic esters, carbonates and carbamates was succesfly developed. The project was realized within the MUSA – Multilayered Urban Sustainability Action – project, funded by the European Union – NextGenerationEU, under the National Recovery and Resilience Plan (NRRP) Mission 4 Component 2 Investment Line 1.5: Strengthening of research structures and creation of R&D “innovation ecosystems”, set up of “territorial leaders in R&D”. References: 1. N. Kumar, N. Goel, Biotechnology Reports, 2019, 24, e00370 2. S.I. Arzola-Rodriguez, L.N. Muñoz-Castellanos, C. Lopez-Camarillo, E. Salas, Biomolecules, 2022, 12, 1897